I cannot let September pass without noting that 34 years ago this month, I arrived at Columbia University to start my laboratory to do research on poliovirus (pictured). That virus is no longer the sole object of our attention – we are wrapping up some work on poliovirus and our attention has shifted elsewhere. But this is a good month to think about the status of the poliovirus eradication effort.

So far this year 26 cases of poliomyelitis have been recorded – 23 caused by wild type virus, and three caused by vaccine-derived virus. At the same time in 2015 there were 44 reported cases of polio – small progress, but, in the words of Bill Gates, the last one percent is the hardest.

One of the disappointments this year is Nigeria. It was on the verge of being polio-free for one year – the last case of type 1 poliovirus in Nigeria had been recorded in July of 2014. In August the government reported that 2 children developed polio in the Borno State. The genome sequence of the virus revealed that it had been circulating undetected in this region since 2011. Due to threats from militant extremists, it has not been possible for vaccination teams to properly cover this area, and surveillance for polioviruses has also been inefficient. The virus can circulate freely in a poorly immunized population, and as only 1% of infections lead to paralysis, cases of polio might have been missed.

The conclusion from this incident is that the declaration that poliovirus is no longer present in any region is only as good as the surveillance for the virus, which can never be perfect as all sources of infection cannot be covered.

Of the 26 cases of polio recorded so far in 2016, most have been in Afghanistan and Pakistan (9 and 14, respectively). It is quite clear that conflict has prevented vaccination teams from immunizing the population: in Pakistan, militants have attacked polio teams during vaccination campaigns.

Recently 5 of 27 sewage samples taken from different parts of the province of Balochistan in Pakistan have tested positive for poliovirus. Nucleotide sequence analysis revealed that the viruses originated in Afghanistan. The fact that such viruses are present in sewage means that there are still individuals without intestinal immunity to poliovirus in these regions. In response to this finding, a massive polio immunization campaign was planned for the end of September in Pakistan. This effort would involve 6000 teams to reach 2.4 million children. Apparently police will be deployed to protect immunization teams (source: ProMedMail).

The success of the polio eradication program so far has made it clear that if vaccines can be deployed, circulation of the virus can be curtailed. If immunization could proceed unfettered, I suspect the virus would be gone in five years. But can anyone predict whether it will be possible to curtail the violence in Pakistan, Afghanistan, and Nigeria that has limited polio vaccination efforts?

India has been free of polio for over one year. This is a remarkable accomplishment, considering that just 30 years ago the country recorded 200,000 cases of the disease annually, or one every three minutes. With polio endemic in two neighboring countries, Pakistan and Afghanistan, and in the more distant Nigeria (figure), can India remain free of the disease? According to Shahnaz Wazir Ali, the Pakistani Prime Minister’s focal person for polio, there is little risk for export of the virus from Pakistan:

The likeliness of polio virus being exported to India from Pakistan is very low, and historically, it has not happened. Those who travel from India to Pakistan are mostly adults. There are rarely any babies. So the chances are low.

It is correct that polio has not traveled from Pakistan to India during the modern era of virus detection (1980 to the present). However, the same genotypes of types 1 and 3 poliovirus have circulated in both countries, implying sharing of viruses some time in recent history. Therefore Ali cannot conclude that export of virus to India ‘has not happened’.

Poliovirus continues to circulate in Pakistan, which shares a border with India: there were 198 cases in that country in 2011, the most of any in the world, and 16 cases so far in 2012. Remember that most poliovirus infections are asymptomatic, so the number of paralytic cases is far lower than the actual number of infections. The ratio of paralytic cases to infections varies according to the viral serotype: 1:200, 1:1800, and 1:1200 for types 1, 2, and 3 respectively. Furthermore, poliovirus has been known to spread from Pakistan from other countries. An outbreak of polio in Xinjiang, China, in 2011 was caused by virus imported from Sindh, Pakistan. There were 21 paralytic cases caused by poliovirus type 1, over half of which occurred in individuals 19-53 years old. The outbreak was halted by immunization but the region remains at risk for importation from Pakistan.

Poliovirus also continues to circulate in Afghanistan, which lies on the northwestern border of Pakistan. Eighty cases of paralytic disease were reported in this country in 2011, and 7 so far in 2012. It has been difficult to control polio in the southern provinces of Kandahar and Helmand due to ongoing armed activities. There is active migration between the southern regions of Afghanistan and Pakistan which has lead to a steady exchange of polioviruses between the two countries.

There many other examples of polio spread from one country to another in recent years. Following cessation of polio immunization in 2003, virus spread from Nigeria to many countries in Africa as well as to Indonesia. From India poliovirus has spread to Nepal, Angola (2005 and 2007), and Tajikistan and then to Russia (2010), in all cases causing substantial outbreaks of the disease.

The message is clear: poliovirus spreads easily among countries, and it is often spread by infected adults, not children. Because poliovirus infection is frequently asymptomatic, such spread cannot be detected by simply examining travelers for signs of paralysis.

For these reasons I am skeptical of Ali’s reassurance that the virus is not likely to spread from Pakistan to India. If adults mainly travel from India to Pakistan, as she says, they could well be infected and import the virus back home before it is detected. Furthermore, adults could bring the virus to India from other countries where poliovirus continues to circulate, although that is not Pakistan’s concern.

Because Pakistan remains a major reservoir of poliovirus, it is a good sign that the country is acknowledging the possibility that they might export the virus to India. The best way to avoid this scenario would be to intensify their immunization programs and eliminate the virus. Apparently Ali has been speaking with Indian officials to learn how they accomplished this goal:

We got to know what actually took India to become polio-free. We have understood the scale and efforts that we require to make Pakistan polio-free.

A new bivalent poliovirus vaccine, consisting of infectious, attenuated type 1 and type 3 strains, has been deployed in Afghanistan. The use of this vaccine was recommended by the Advisory Committee on Poliomyelitis Eradication, the global technical advisory body of the Global Polio Eradication Initiative. Considering the polio experience in Nigeria, the elimination of type 2 poliovirus from the vaccine might have serious consequences.

There are three serotypes of poliovirus, all of which can cause poliomyelitis. Infection with one serotype of the virus does not confer protection against the other two; therefore poliovirus vaccines have always included all three serotypes (they are trivalent). The attenuated vaccine that is used in the eradication effort is an infectious vaccine. The vaccine is ingested, the viruses replicate in the intestine, and immunity develops. Viruses of all three serotypes undergo genetic changes during replication in the alimentary tract. As a consequence, the vaccine recipient excretes polioviruses that can cause paralysis. These so-called vaccine-derived polioviruses (VDPV) can cause outbreaks of poliomyelitis in non-immune people, as described in Polio among the Amish.

Poliovirus type 2 was declared eradicated from the globe by the World Health Organization in 1999. When type 2 poliovirus was eliminated, many countries began using monovalent type 1 and type 3 vaccines: one vaccine for type 1 and another for type 3. As a consequence of this immunization strategy, population immunity to type 2 poliovirus declined. Not unexpectedly, there was an outbreak of type 2 poliovirus in Nigeria in 2006. The surprise was that the outbreak was caused by a poliovirus type 2 vaccine strain.

Before 2003, the year that Nigeria began a boycott of polio immunization, the trivalent polio vaccine was used. Immunization resumed with monovalent types 1 and 3 vaccine in 2004. Therefore the source of the VDPV type 2 is most likely the trivalent vaccine used before 2003.

The press release at polioeradication.org announcing the bivalent vaccine proclaims:

Of the three wild polioviruses (known as types 1, 2 and 3), type 2 has not been seen anywhere in the world since 1999.

The statement ignores the fact that there is vaccine-derived type 2 poliovirus in the world – and it can cause polio as well as ‘wild’ poliovirus. Such strains have been isolated in Nigeria as recently as October 2009. Why isn’t the type 2 vaccine being used in Afghanistan when it is very likely that vaccine-derived type 2 poliovirus is still circulating? Just because we haven’t isolated type 2 poliovirus recently doesn’t mean that it’s gone. No type 2 poliomyelitis was detected in 1999, yet the vaccine-derived virus was silently circulating in humans.

What will be the WHO response to an outbreak of type 2 polio in Afghanistan? They will probably deploy trivalent vaccine, as was done in Nigeria in 2006. But this approach will simply lead to another cycle of eradication and emergence of type 2 polio. It’s time to begin using inactivated poliovirus vaccine, which I’ve been dreaming about for some time.